Neurotransmitter levels in the basal ganglia are associated with intracortical circuit activity of the primary motor cortex in healthy humans

Abstract

Background: The basal ganglia are strongly connected to the primary motor cortex (M1) and play a crucial role in movement control. Interestingly, several disorders showing abnormal neurotransmitter levels in basal ganglia also present concomitant anomalies in intracortical function within M1.

Objective/hypothesis: The main aim of this study was to clarify the relationship between neurotransmitter content in the basal ganglia and intracortical function at M1 in healthy individuals. We hypothesized that neurotransmitter content of the basal ganglia would be significant predictors of M1 intracortical function.

Methods: We combined magnetic resonance spectroscopy (MRS) and transcranial magnetic stimulation (TMS) to test this hypothesis in 20 healthy adults. An extensive TMS battery probing common measures of intracortical, and corticospinal excitability was administered, and GABA and glutamate-glutamine levels were assessed from voxels placed over the basal ganglia and the occipital cortex (control region).

Results: Regression models using metabolite concentration as predictor and TMS metrics as outcome measures showed that glutamate level in the basal ganglia significantly predicted short interval intracortical inhibition (SICI) and intracortical facilitation (ICF), while GABA content did not. No model using metabolite measures from the occipital control voxel was significant.

Conclusions: Taken together, these results converge with those obtained in clinical populations and suggest that intracortical circuits in human M1 are associated with the neurotransmitter content of connected but distal subcortical structures crucial for motor function.

Keywords: GABA; Globus pallidus; Glutamate; MRS; Putamen; SICI; TMS.